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Biomedical subjects

C Cannistraci

Publications and source records attributed to C Cannistraci.

At least 19 recordsLinked to original sources

Scavenging effects of terbinafine on free radicals in vitro.

One of the goals of antifungal therapy is to combine an anti-inflammatory activity with antimycotic properties, and therefore it is interesting to evaluate the capacity of active antifungal drugs to interfere with different phases of the inflammatory reaction. In order to identify a possible scavenger property of free radical species of the antifungal agent terbinafine, we studied its activity on the reduction of nitrotetrazolium blue chloride (NTB), induced by superoxide anions with the ultraviolet (UV)- and chemical-induced peroxidation of unsaturated lipid targets. NTB reduction was followed by spectrophotometer and the decomposition of squalene or methyl arachidonate by gas chromatography-mass spectrometry. Terbinafine (20 microgram and over) was capable of significantly inhibiting NTB reduction, indicating that the drug scavenges superoxide anion radicals. In these conditions no modifications of the concentration of the drug, as evaluated by high performance liquid chromatography, were observed. The UV- or chemically induced peroxidation of squalene and arachidonic acid was significantly reduced in the presence of 50 microgram of terbinafine, suggesting that the substance interferes with the chemical properties of peroxyl radicals. In all the tests used the degree of inhibition was proportional to the amount of free radicals generated. In conclusion our results indicate that terbinafine, at therapeutic concentrations, can be considered to be a free radical interceptor in vitro and could exert a mild anti-inflammatory activity in vivo.

Allylamine↗

Thimerosal positivities: patch testing to methylmercury chloride in subjects sensitive to ethylmercury chloride.

The aim of this paper was to evaluate whether methylmercury chloride (MeHgCl) aq., when patch tested in a group of thimerosal-positive subjects reacting to ethylmercury chloride (EtHgCl), might be a reliable model for the better understanding of interactions between alkylmercury compounds and the skin. 19 out of 21 consecutive patients who previously had given positive patch-test reactions to both ethylmercury chloride 0.0165% eth.(EtHgCl, 0.615 mM) and MeHgCl 0.031% aq.(1.23 mM), and negative reactions to thiosalicylic acid 0.05% (3.24 mM) aq./eth. 50/50, were repatch tested to 8 microl of MeHgCl 0.031% aq. and to 8 microl of aq. solutions containing MeHgCl mixed with cysteine, glutathione, ZnSO4, MgSO4, MnSO4, ZnCl2, MgCl2 and MnCl2, respectively. The results showed that cysteine, glutathione and Zn(II) salts were able to abolish the positive reactions, demonstrating the rôle played by both thiol groups and Zn(II) itself. Patch tests concomitantly carried out in 16 out of 19 patients to 8 microl of aqueous MeHgCl and to 8 microl of aqueous solutions containing MeHgCl and MeHgCl mixed to fragment 56-61 of metallothionein I (MT I), MT I and MT II-Zn, respectively, revealed that all the MTs tested were able to reduce or to inhibit the reactions, demonstrating the effect of the thiol groups. Due to the close chemical similarities to EtHgCl and to its water solubility, MeHgCl seems to be a suitable model for evaluating the reactivity of alkylmercury compounds in the skin. We speculate that both EtHg- and MeHg-derivatives are xenobiotics with similar reactivity. However, the lack of clinical relevance of the reactions to both alkyl compounds lead us to conclude that, since environmental exposure does not seem to play a pivotal rôle, they probably have mostly to do with compounds included in in the standard series, and are elicited by reduced function of physiological SH chelators.

Adult↗

Thimerosal positivities: the role of organomercury alkyl compounds.

Contact allergy to thimerosal (TH) has not been considered a marker for mercury allergy, since there is a low degree of cross-sensitivity to inorganic as well as to organic mercury salts. 40 subjects, who previously gave a positive patch test reaction only to thimerosal 0.1% pet. (Hermal), when simultaneously repatch-tested to solutions containing TH, mersalyl acid, p-amino-phenylmercuric acid, mercuric acetate and thiosalicylic acid, respectively, gave positive reactions only to TH. 36 out of 40 subjects were divided into 2 groups of 18 subjects and simultaneously repatch-tested to solutions containing TH, methylmercury chloride (MeHgCl), thiosalicylic acid, and, ethylmercury chloride (EtHgCl), respectively. EtHgCl was tested in the 1st group at 0.031% and in the 2nd group at 0.015%. The results showed that all subjects gave concomitant positive reactions to TH, EtHgCl and MeHgCl. EtHgCl 0.031% gave a higher number of reactions than EtHgCl 0.015%, underlining the rôle of the solvent in these reactions. Patch test results in 300 consecutive patients to a standard series, to which MeHgCl was added, showed that MeHgCl and TH were never able to give isolated positive reactions, and that the concomitant positive reactions occurred in only 3.6% of subjects. In conclusion, our data seem to suggest that the positive reactions to TH found in our patients were due to EtHgCl, and that the structural similarities with MeHgCl were so close that the skin reacted against each as if they were identical.

Alkylation↗

Thimerosal positivities: the rôle of SH groups and divalent ions.

For a better understanding of the mechanistic details of the interactions of organomercury compounds inside the skin, 32 subjects who previously had given positive patch-test reactions to thimerosal (TH) and negative reactions to thiosalicylic acid, were divided into 2 groups. 16 subjects were repatch tested to ethylmercury chloride (EtHgCl) and to solutions containing EtHgCl mixed with L-cysteine and glutathione, respectively. The remaining 16 were repatch tested to EtHgCl and to solutions containing EtHgCl mixed with chlorides of Zn, Mg, and Mn, respectively. The results showed that whilst L-cysteine, glutathione and ZnCl2 were able to abolish or to reduce the positive reactions to EtHgCl, chlorides of Mg and Mn were unable to do so. Patch tests revealed that in causing positive reactions to TH, EtHg probably interacted with thiol groups and with Zn ions, as in biological systems when causing toxic effects. The limited number of TH reactions in the general population, the constant presence of concomitant positive reactions to EtHgCl and MeHgCl, and the lack of cross-reactivity with other organic or inorganic mercury compounds, lead us to speculate that reactions to TH are due to organomercury alkyl compounds, and that positive subjects have a constitutively reduced capability to metabolize organomercury compounds, rather than to reveal previous exposure.

Alkylmercury Compounds↗

The influence exerted by cutaneous ligands in subjects reacting to nickel sulfate alone and in those reacting to more transition metals.

To study the influence exerted by cutaneous ligands in nickel reactions we have evaluated the patch tests responses to 4 aqueous nickel salts (sulfate, chloride, nitrate, acetate) able to form different complexes with different geometry. Two groups of respectively 71 subjects who previously reacted only to nickel sulfate 5% petrolatum (pet) and of 30 subjects who previously reacted to nickel sulfate 5% pet and to at least 1 other transition metal, were simultaneously repatch-tested to 200 microg of Ni++ contained in nickel sulfate in pet and to 47 microg of Ni++ contained in 4 different aqueous nickel salts. Another 2 groups of 25 subjects with the same characteristics were simultaneously repatch tested to 200 microg of Ni++ in pet and to 12 microg of aq Ni++ as in the first 2 groups. Visual score, total score, and mean value of the reactions were utilized in evaluating the degree of the responses. On testing to 200 microg of Ni++ in pet all the subjects were able to give positive responses. Whilst a higher percentage of the responses of 2+ degrees was found in subjects reacting to nickel sulfate 5% pet alone, a higher percentage of responses of 3+ degrees was observed in subjects reacting to more transition metals. On testing to 47 and 12 microg of aqueous Ni++ a large variability of responses to the single salts was observed in all the subjects. However, in subjects reacting to more metals there were either a greater number of multiple responses to 3 or 4 salts or responses stronger than those found in subjects reacting to nickel sulfate alone. Although patch testing cannot give us complete information about the degree of previous exposure, the results arising from the tests seem to demonstrate that the subjects allergic to nickel and other transition metals are more reactive than the subjects allergic only to nickel to the application of the same amounts of Ni++ contained in different salts. When considering the QSAR model, the difference in the sensitizing potential of the metal at the same penetration properties can depend on the possibility of combining with specific ligands. Therefore, it is likely that in subjects reacting to more metals there is a more uniform availability of cutaneous ligands which conditions the formation of complexes more immunogenic. The arising inflammatory reaction in these cases leads to a stronger but less specific response.

Analysis of Variance↗

Multiple sensitivities to transition metals: the nickel palladium reactions.

Patch test data of 1000 consecutive patients sensitive to at least 1 substance of our standard series showed that transition metals gave associated reactions amongst themselves more frequently than they did with the remaining substances. The responses to transition metals were largely variable and seemed dependent not only upon the associated exposure to different metals or the concomitant responses of the T cell clones, as reported by others, but also upon the chemical properties of the metals and the consequent interactions inside the skin. Concomitant reactions to nickel sulfate and palladium chloride were the most frequently found associated positivities and occurred in a minority of nickel-sulfate-sensitive subjects. In 43 out of 45 of these subjects, patch tests to mixed solutions containing nickel sulfate, plus sulfates of magnesium, zinc, and manganese at higher doses, were not able to reduce the nickel sulfate reactions. This behaviour contrasted with that found in the majority of subjects sensitive only to nickel sulfate. These findings seem to demonstrate that, whilst in subjects with positive reactions to nickel sulfate alone antigen formation involves biomolecules containing ions, in those with concomitant reactions to palladium chloride, other structures are involved.

Chlorides↗

Interactions of sulfates of divalent metals in nickel-sulfate-sensitive patients.

70 nickel-sensitive subjects who previously gave positive patch test response to 10 microliters of nickel sulfate 0.1 M, were patch tested to 10 microliters of mixed aqueous solutions containing nickel sulfate 0.1 M+magnesium sulfate 0.3 M, nickel sulfate 0.1 M+zinc sulfate, 0.3 and 0.5 M, respectively, nickel sulfate 0.1 M+ manganese sulphate 0.3 and 0.5 M, respectively nickel sulphate 0.1 M+ cadmium sulfate 0.1 and 0.3 M, respectively, nickel sulfate 0.1 M+iron sulfate (III) 0.1 and 0.3 M, respectively, and to 10 microliters of aq. cadmium sulfate 0.1 M, aq. cadmium sulfate 0.3 M, aq. iron sulfate 0.1 M, aq. iron sulfate 0.3 M. The results showed that, whilst sulfates of divalent metals with similar size and redox properties (Mg, Zn and Mn) were able to reduce or to suppress, in a dose-dependent way, the majority (75%) of nickel reactions, those with large radius and different oxidation state(Fe III), generally gave an increase in the reactions. In about 15% of the tested subjects, an increase in all the positive reactions to the mixed solutions was found. The findings seem to demonstrate that in only a majority but not all of nickel sulfate allergic reactions, is Ni(II) able to substitute for divalent ions with similar properties at the ion sites of some proteins. This tendency reproduces the results of experimental systems, in which nickel toxicity and cancerogenity are considered responsible. In contrast, in about 15% of the tested subjects, there was a general enhancement of the reactions. In these cases, either the occurrence of a "hyper-irritable" skin caused by the adopted test system or, more likely, the formation of Ni complexes with different geometries, is hypothesized.

Adult↗

Nickel chloride/chlorides of divalent metal interactions in nickel-sensitive subjects.

To verify if the counter-ion Cl- permits the same interactions between nickel and divalent metals with physicochemical similarities as the counter-ion SO4- does, 50 sensitive subjects to nickel sulfate 5% pet. who previously gave positive patch test reactions either to 8 mu 1 of aq. nickel sulfate 0.1 M or to 8 mu 1 of aq. nickel chloride 0.1 M, or to both, were patch retested simultaneously to 8 mu 1 of, respectively, aq. nickel sulfate 0.1 M and aq. nickel chloride 0.1 M, and to 8 mu 1 of aq. mixed solutions containing, respectively, nickel chloride 0.1 M+magnesium chloride 0.3 M, nickel chloride 0.1 M+zinc chloride 0.3 M, nickel chloride 0.1 M+zinc chloride 0.5 M, nickel chloride 0.1 M+manganese chloride 0.3 M, and nickel chloride 0.1 M+manganese chloride O.5 M. Whilst 4 subjects gave a positive patch test response to only nickel sulphate, 8 gave a positive response to nickel chloride alone and the remaining 38 gave a concomitant positive response to both. In all subjects who gave positive responses to nickel chloride, the chlorides of divalent metals were not able to inhibit or reduce the positive reaction. 25 healthy subjects patch tested to both single salts and mixed solutions, and all gave negative responses. 9 of the 50 subjects, 4 who previously gave positive reactions to only nickel chloride 0.1 M, and 5 with concomitant reactions of equal intensity to both nickel chloride and nickel sulfate 0.1 M, were patch retested simultaneously to 8 mu 1 of, respectively, aq. nickel sulfate 0.1 M, aq. nickel chloride 0.1 M and aq. mixed solutions containing nickel sulfate (0.1 M) mixed with sulfates (0.3 M) and nickel chloride (0.1 M) mixed with chlorides of Mg, Zn, Mn (0.3 M). Whilst the mixed sulfate solutions were able to reduce nickel sulfate, 0.1 M patch test positive reactions, those containing chlorides, at all concentrations tested, did not inhibit the nickel chloride reactions in any of the subjects. The results of the tests to chlorides, compared to those reached on testing to sulfates of the same metals, lead us to hypothesize that the anion probably affects the uptake and local tissue distribution of the metal, modulating in this way, together with the individual cutaneous ligands, its effects.

Adult↗

Nickel/magnesium interactions in nickel-sensitive patients.

Experimentally demonstrated interactions between Ni2+ and Mg2+ were examined in human beings. 110 subjects patch-test-positive to 10 microliters aq. NiSO4 0.1 M were subdivided into groups of 30, 50 and 30 people. Each subgroup was tested to 10 microliters NiSO4 0.1 M solution as a control and to mixed solutions containing NiSO4 0.1 M together with, respectively MgSO4 0.1 and 0.3, 0.3 and 0.5 and 0.5 and 1 M. On increasing the applied concentrations of MgSO4, the % of patients with reduced or suppressed nickel reactions, with 1 exception, proportionally increased. The exception concerned testing with 0.5 M, where a paradoxically exacerbating increase in nickel reactions was seen in a majority of nickel-sensitive subjects. MgCl2 aq. at 0.3, 0.5 and 1 M concentrations was not able to reduce the cutaneous patch test positive reactions to NiCl2 0.1 M in 25 sensitive patients. On increasing the applied concentrations of MgCl2, both the number and intensity of patch test reactions to NiCl2 proportionally increased. A supposed rôle of the sulfate and chloride counterions in the penetration of nickel was examined in 30 NiSO4 5% patch-test-positive patients, testing to 10 microliters of aq. NiSO4 0.1 M, NiCl2 0.1 M, NiSO4 0.1 M + MgCl2 0.3 M, NiCl2 0.1 M + MgSO4 0.3 M, Na2SO4 0.3 M, NaCl 0.3 M, NiSO4 0.1 M + Na2SO4 0.3 M, NiCl2 0.1 M + NaCl 0.3 M. The findings suggest that the addition of sulfate or chloride to nickel could determine the formation of different Ni complexes directed toward different targets, one Mg(2+)-dependent, the other Mg(2+)-independent.

Adult↗

Interaction of palladium ions with the skin.

87 subjects sensitive to both nickel sulfate and palladium-chloride pet., were contemporaneously patch retested to nickel sulfate 5% pet., metallic palladium chloride 1% pet. and to palladium chloride 1% aq. Whilst all subjects reacted to nickel sulfate and palladium chloride pet., only 3 reacted to palladium chloride aq. No positive reactions were found to metallic palladium. The negative results to palladium chloride aq. are probably due to the formation of a new palladium ion (PdCl4)2-, achieved on adding an amount of hydrocloric acid to the aqueous solution of PdCl2. The findings seem to demonstrate that the allergic reaction to palladium depends on the arrangement of the metal electrons. The sensitization to palladium does not seem to be dependent on the element itself but on the complexes formed by the different compounds. The concomitant reactions to nickel and palladium ions could be dependent on the generation of similar complexes between the ions and the skin proteins.

Dermatitis, Allergic Contact↗

Serum and urine concentrations in nickel-sensitive patients after prolonged oral administration.

8 nickel-sensitive subjects were given a gradually increasing daily oral intake of NiSO4 in water. The exposure lasted from between 91 and 178 days and the total intake ranged from between 113 and 278 mg of Ni++. While 6 subjects were continuously exposed over the entire period, the other 2 were exposed for 2 shorter periods with an interval between the 2 exposures of 84 and 63 days, respectively. Nickel exposure was well tolerated by all subjects, and there was no worsening of the cutaneous manifestations. Ni++ serum and urine concentrations were repeatedly assayed. A reduction of intestinal adsorption and an activation of the renal excretion were shown through an evaluation of the ratios of Ni++ serum concentration/Ni++ cumulative oral intake, Ni++ urinary amount/nickel cumulative oral intake and Ni++ serum amount/Ni++ urine amount. The course of Ni++ faecal amounts, calculated indirectly, increased rapidly in time and was consistent with the other courses. In many subjects, the decrease in serum concentrations was followed by a slight increase. It is likely that this phenomenon is due to the release of epidermally stored nickel. These data seem to indicate that in some sensitive subjects, prolonged oral exposure to NiSO4 in water reduces the intestinal adsorption of nickel and activates its renal excretion, also promoting the mobilization of accumulated element.

Administration, Oral↗

Hypertrophic allergic contact dermatitis from hair dye.

We report a case of hypertrophic allergic contact dermatitis probably due to p-phenylenediamine (PPDA) in a 26-year-old female, which developed at the sites of application of a black hair dye to the skin. Histological examination revealed an eczematous process. The lesions subsided completely except for leukoderma that remained on the leg. Patch tests showed positive reactions to PPDA, p-aminophenol and Disperse Orange 3. PPDA, which was one of the components of the dye, was considered to be the primary sensitizer because it was the only substance able to reproduce at the patch test site both the hypertrophic pattern and the permanent leukoderma found in the patient's lesions. To explain the difference in reaction between PPDA and the other 2 para-group substances, we speculate that they are due to different quantities of reactive intermediates, oxidation products and free radicals, produced by these substances.

Adult↗

Interaction of metals in nickel-sensitive patients.

Nickel (Ni) dermatitis is thought to involve the formation of complexes between Ni ions and suitable proteins. 4 groups of 30 subjects who gave positive patch test responses to NiSO4 2.9% aq. were each retested to 1 of 4 different solutions containing equimolar (0.1 M) amounts of NiSO4 plus MgSO4, NiSO4 plus CuSO4, NiSO4 plus ZnSO4, and NiSO4 plus Li2SO4, respectively. The results, evaluated at 2 days by visual scoring only, demonstrated that the 4 metals exerted a different influence on the nickel reactions, perhaps interfering with one or more factors affecting the formation of Ni+ + complexes.

Copper↗